Integrated Clinical Scale Manufacturing System for Cellular Products Derived by Magnetic Cell Separation, Centrifugation and Cell Culture

Abstract

Manufacturing of cellular products for therapeutic purposes like stem cell or cancer therapy requires equipment with specific characteristics not always addressed by conventional technologies. A new integrated cell processing device is presented that can handle all current technical requirements for manufacturing cellular products by automation of the complete process in a GMP‐compliant single‐use tubing set. Its capabilities are exemplified in the presented study by successful processing of adult stem cells, natural killer cells, and several cell lines. Multiple cell processing workflows can be automated in a functionally closed environment: from cell separation through cell culture to formulation of the final product.

Biomanufacturing of Therapeutic Cells: State of the Art, Current Challenges, and Future Perspectives

“…Simplifying the process and avoiding unnecessary open steps will be necessary. An example of such an integrated cell production device consisting of an automated centrifugation unit, the magnetic-activated cell sorting (MACS) separation unit, and cell cultivating unit was developed (90). Complicated processing steps, such as preparation of enriched cell populations, washing, labeling, transduction, expansion, separation, sampling, and final formulation, could be achieved by automated processes in a GMP-compliant single-use tubing set (90).…”

Automated manufacturing of chimeric antigen receptor T cells for adoptive immunotherapy using CliniMACS Prodigy

“…Various culture vessels, including G-Rex flasks (Wilson Wolf Manufacturing), cell differentiation bags and bioreactors have proven suitability for T-cell manufacturing [5][6][7]. Current procedures involve a variety of hands-on steps and transfer of cells between cultivation vessels, each bearing the risk of contamination, human errors and cell loss.To simplify the protocol and minimize potential risks during the process, the CliniMACS Prodigy [8] has been adapted to automate clinical-scale manufacturing of cell products [9][10][11]. This platform allows for magnetic beadbased cell separation followed by activation, transduction, multiple media-exchanges and washing steps with a single-use, closed tubing system ( Figure 1A, Figure 1B).…”

Recent Developments in Cellular Immunotherapy for HSCT-Associated Complications

“…Suitable bioreactors for MSC expansion on the market are the Quantum ® (Terumo) and Scinus Cell Expansion™ (Xpand Biotechnology). In addition, the CliniMACS Prodigy ® (Miltenyi Biotec) allows automated cell processing starting from sample preparation to cell culture and magnetic cell separation until the final formulation of the cellular product in a closed system by using single-use tubing sets (60). The instrument has the capability for preparation of mononuclear cells from BM samples using high-density gradient centrifugation prior to cell expansion.…”

“…To guarantee robust and reliable processes as well as safe and effective clinical products, a standardization of the cell manufacturing is essential, which can be accomplished by automation. A newly developed cell processing device, the CliniMACS Prodigy ® , enables to run the complete CCS in an automated and closed system (60, 147). The cells are processed from the first until the last step within a closed and single-use tubing set.…”

“…Additionally, each device demands installations, services, qualifications, and training of operators. A new device, the CliniMACS Prodigy ® instrument (Miltenyi Biotec), is designed as an all-in-one solution for automated cell processing in a closed GMP-compliant system (60). A process specifically developed and optimized for the manufacture of CAR T cells on this instrument is now available.…”